We have established a CRADA to prospectively validate the diagnostic accuracy of a lung cancer early detection approach. A clinical team of investigators from 11 institutions throughout the United States and Canada is accruing stage I resected lung cancer patients to a protocol where annual induced sputums will be acquired and immunostained. Ongoing patient followup will permit the eventual correlation of immunostaining status with clinical outcome (correlation of positive immunostaining with the development of lung cancer and vice versa). Immunostaining for this study will be done at the University of Pennsylvania, and data acquisition and analysis will be handled at Johns Hopkins University. As part of this effort, selected patients will undergo bronchoscopy, and their bronchial lavage fluids will be studied for the quantity and quality of growth factor expression. We have developed a variety of methods for assessing the proliferative capacity of bronchial lavage products in an effort to complement the sputum immunocytology approach in determining who is and is not at risk for manifesting lung cancer. An archive of sputum and other clinical specimens remaining after the primary analysis will be conserved to permit rapid analysis of other new promising early detection markers. All CRADA funds are being expended to support the clinical trial, and none of these funds are being spent at the NCI. Core analysis includes quantitation of autocrine growth factors such as GRP as well as more global assessment of neuroendocrine activation by monitoring levels of peptidyl amidating monooxygenase (PAM) activity. This application builds upon the biology elucidated in our lab, establishing the role of this enzyme system in contributing to the chronic growth stimulation of neoplastic pulmonary epithelium. This work has major relevance in developing new early lung cancer detection approaches.